The development of a durable, hemocompatible valve prosthesis is the long-term objective of this proposal. While heart valve prostheses have been used successfully since 1960, 10-year survival rates still range from 37-58%. Existing replacement valves are either mechanical or biological. Bioprostheses suffer from time dependent structural changes leading to valve failure, while mechanical valves are subject to thrombus deposition and subsequent complications resulting from emboli. A valve offering the hemocompatibility of bioprostheses and the durability of mechanical valves would provide a superior alternative to those currently approved for clinical use. ABIOMED's polyurethane trileaflet valve has demonstrated excellent durability and hemocompatibility in clinical evaluation of the AbioCor replacement heart. The goal of this Phase I project is the development of a trileaflet heart valve prosthesis with low trans-valve pressure loss. The proposed work involves adapting the existing 24mm ABIOMED valve design to the requirements of a smaller, 21mm prosthetic valve, which is the most frequently used size in replacement surgeries. This work also includes in vitro performance characterization and accelerated valve cycling, as well as computer simulation using a novel computational fluid dynamics package. In Phase II, the valve design will be optimized, and hemocompatibility will be assessed through in vivo animal experiments.